Contents 1 Nanotechnology and Its Drug Delivery Applications... 1 1.1 Introduction... 1 1.2 Historical Prospects of Nanotechnology... 2 1.3 Promising Role in Drug Delivery... 3 1.3.1 Nanoparticles and Drug Delivery... 8 1.3.2 Use of NPs Formulation in Drug Delivery... 9 1.3.3 Cellular and Intracellular Targets... 11 1.3.4 The Brain The Ultimate Target for Drug Delivery... 12 1.4 Innovations in Nanotechnology... 14 1.5 Nanotechnology Theory to Applications... 16 1.6 Nanomedicine/Nanoscience/Nano-Engineering and Relationship with Drug Delivery... 19 1.6.1 Nanomedicine and Drug Delivery... 19 1.6.2 Nanoengineering and Drug Delivery... 21 1.7 Types of Nanodelivery: Natural or Synthetic... 23 1.7.1 Synthetic Polymers... 23 1.7.2 Natural Polymers... 23 1.8 Natural and Synthetic Polymeric Nanoparticles... 24 References... 27 2 Nanoparticles Types, Classification, Characterization, Fabrication Methods and Drug Delivery Applications... 33 2.1 Introduction... 34 2.2 Classification of Nanoparticles... 40 2.3 Characterization of Nanoparticles... 40 2.3.1 Particle Size... 40 2.3.2 Surface Charge... 43 2.3.3 Surface Hydrophobicity... 44 2.3.4 Drug Release... 44 v
vi Contents 2.4 Preparation of Nanoparticles... 44 2.4.1 Solvent Evaporation Method... 45 2.4.2 Spontaneous Emulsification or Solvent Diffusion Method... 46 2.4.3 Double Emulsion and Evaporation Method... 46 2.4.4 Salting Out Method... 46 2.4.5 Emulsions- Diffusion Method... 47 2.4.6 Solvent Displacement/Precipitation Method... 48 2.4.7 Coacervation or Ionic Gelation Method... 48 2.4.8 Polymerization Method... 49 2.4.9 Production of Nanoparticles Using Supercritical Fluid Technology... 49 2.5 Most Favorable Requirements for Designing Therapeutic Nanoparticles... 50 2.6 Types of Pharmaceutical Nanosystems... 51 2.6.1 Carbon Based Structures... 51 2.6.2 Fullerenes... 53 2.6.3 Quantum Dots... 54 2.6.4 Nanoshells... 56 2.6.5 Nanobubbles... 57 2.6.6 Paramagnetic Nanoparticles... 58 2.6.7 Nanosomes... 59 2.6.8 Pharmacyte... 60 2.6.9 Dendrimers... 61 2.6.10 Nanopores... 64 2.6.11 Microbivores... 65 2.6.12 Nanocrystals and Nanosuspension... 65 2.6.13 Solid Lipid Nanoparticles... 66 2.6.14 Silicon-Based Structures... 67 2.6.15 Metallic Nanoparticles... 68 2.6.16 Liposomes... 68 2.6.17 Polymeric Micelles... 69 2.6.18 Polymer Drug Conjugate... 70 2.6.19 Polyplexes/Lipopolyplexes... 70 2.6.20 Respirocytes... 70 2.6.21 Polymeric Nanoparticles... 71 2.6.22 Applications of Nanoparticulate Delivery Systems... 73 2.6.23 Passive Targeting... 74 2.6.24 Active Targeting... 74 2.6.25 Tumor Targeting Using Nanoparticulate Delivery Systems... 76 2.6.26 Long-Circulating and Target-Specific Nanoparticles... 77 2.6.27 Nanoparticles for Oral Delivery of Peptides and Proteins... 79 2.6.28 Nanoparticles for Gene Delivery... 80
Contents vii 2.6.29 Nanoparticles for Drug Delivery into the Brain... 81 2.6.30 Anthrax Vaccine Uses Nanoparticles to Produce Immunity... 82 2.6.31 Stem Cell Therapy... 83 2.6.32 Gold Nanoparticles Detect Cancer... 83 2.7 Hazards and Toxicity Profile of Nanoparticles... 85 2.7.1 Health Implication of Nanoparticles... 85 References... 88 3 Natural Polymers vs Synthetic Polymer... 95 3.1 Bioengineered Materials: Nano-Engines of Drug Delivery Systems... 95 3.2 Polymeric Nanoparticles... 96 3.3 Contemporary Methodologies for Fabrication of Polymeric Nanoparticles... 97 3.4 Activation-Modulated Drug Delivery: Environmental Activation/Stimuli Responsive Smart Delivery System... 98 3.5 Time to Move on Innovative Methods of Administration... 100 3.6 History of Drug Delivery from the Ancient to Date... 102 3.6.1 Historical Role of Polymers as Plastics... 105 3.7 Shift from Nature to Synthetic (Including the Merits and Demerits of Synthetic Polymers)... 106 3.7.1 Natural Polymers and Synthetic Polymers for Scaffolds... 109 3.7.2 Natural vs Synthetic Polymer (as Biomaterial)... 110 3.7.3 Natural vs Synthetic Polymer in Tissue Engineering... 112 3.7.4 Natural vs Synthetic Polymer Hydrogels... 113 3.8 Natural Polymers (Reasons for Reverting to Nature)... 114 3.8.1 Need of Natural Polymers... 115 3.8.2 Disadvantages of Herbal Polymers... 116 References... 116 4 Plant Derived Polymers, Properties, Modification & Applications... 119 4.1 Introduction... 119 4.2 Sources of Plant Polymers... 121 4.3 Methods of Extractions... 124 4.3.1 Cold Extraction... 124 4.3.2 Hot Extraction [Mild Acidic (EHA), Alkaline (EHB) and Radical Hydrolysis (EHR)]... 125 4.3.3 Radical Hydrolysis (EHR)... 125 4.3.4 Microwave Assisted Extraction (EM)... 125 4.3.5 Ultrasonic Extraction (EU)... 126 4.3.6 Enzymatic Hydrolysis (EE)... 126 4.4 Chemical Composition Analysis... 126 4.5 Physical Properties... 126 4.5.1 Determination of Gelling Strength (GS)... 126 4.5.2 Determination of Gelling Temperature (GT) and Melting Temperature (MT)... 126
viii Contents 4.5.3 Viscosity Measurement (VS)... 127 4.5.4 Molecular Mass Determination (MM)... 127 4.6 Physical-Chemical Modification of Plant Based Natural Polymers (PBNPS)... 127 4.6.1 Chemical Modifications of Plant Based Natural Polymers (PBNPS)... 128 4.6.2 Procedure for the Development of Microfibrillated Plant Based Polymers (MPBPS) by Physical Modification... 134 4.6.3 Pre-treatment... 138 4.6.4 Post-treatments... 139 4.6.5 Dual Modifications... 140 4.6.6 Ozonation... 142 4.7 Genetic/Biotechnology Modification... 143 4.8 Applications of Plant Based Polysaccharides... 144 4.8.1 Cellulose... 144 4.8.2 Hemicellulose... 152 4.8.3 Starches... 153 4.8.4 Pectin... 154 4.8.5 Inulin... 155 4.8.6 Rosin... 156 4.8.7 Plant Based Gums... 157 References... 164 5 Marine Polysaccharides Based Nano- Materials and Its Applications... 185 5.1 Introduction... 185 5.2 Polysaccharides Derived from Marine Sources... 186 5.2.1 Marine Algae Based Polysaccharides... 189 5.2.2 Marine Crustaceans Derived Polysaccharides... 192 5.3 Nanomaterials Derived from Marine Sources... 193 5.3.1 Nano Scaffolds Derived from Fucoidan... 194 5.3.2 Alginate Nanoparticles... 196 5.3.3 Carrageenan Based Nanoparticles... 197 5.3.4 Agarose Nanoparticles... 200 5.3.5 Porphyran Based Nanoparticles... 201 5.3.6 Nanofibers of Ulvan... 202 5.3.7 Mauran Based Nanoparticles... 203 5.3.8 Chitin and Its Nanoparticles... 203 5.3.9 Chitosan Based Nanoparticles... 204 5.3.10 Chitooligosaccharide Based Nanoparticles... 206 5.4 Marine Polysaccharide-Based Nanomaterials and Its Biomedical and Biotechnological Applications... 208 5.4.1 Biomedical Applications of Marine Polysaccharides... 208 5.4.2 Role of Marine Based Polysaccharides for Biotechnological Applications... 212 5.5 Marine Polysaccharide-Based Nanomaterials and Its Patents... 213 References... 213
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